Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: PYGL

Gene summary for PYGL

Gene summary.

Gene information	Species	Human
	Gene symbol	PYGL
	Gene ID	5836
	Gene name	glycogen phosphorylase L
	Gene Alias	GSD6
	Cytomap	14q22.1
	Gene Type	protein-coding
	GO ID	GO:0000272
	UniProtAcc	P06737

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
5836	PYGL	CA_HPV_2	Human	Cervix	CC	9.61e-06	2.43e-01	0.0391
5836	PYGL	CCI_2	Human	Cervix	CC	7.27e-04	7.29e-01	0.5249
5836	PYGL	Tumor	Human	Cervix	CC	9.61e-43	8.14e-01	0.1241
5836	PYGL	sample3	Human	Cervix	CC	1.37e-56	9.35e-01	0.1387
5836	PYGL	T3	Human	Cervix	CC	1.22e-59	9.25e-01	0.1389
5836	PYGL	LZE4T	Human	Esophagus	ESCC	6.43e-19	6.22e-01	0.0811
5836	PYGL	LZE7T	Human	Esophagus	ESCC	2.76e-04	3.18e-01	0.0667
5836	PYGL	LZE20T	Human	Esophagus	ESCC	1.42e-07	3.89e-01	0.0662
5836	PYGL	P4T-E	Human	Esophagus	ESCC	2.45e-12	8.13e-02	0.1323
5836	PYGL	P5T-E	Human	Esophagus	ESCC	5.14e-24	5.90e-01	0.1327
5836	PYGL	P8T-E	Human	Esophagus	ESCC	1.19e-06	2.04e-02	0.0889
5836	PYGL	P9T-E	Human	Esophagus	ESCC	8.70e-15	3.24e-01	0.1131
5836	PYGL	P10T-E	Human	Esophagus	ESCC	1.46e-13	4.30e-01	0.116
5836	PYGL	P11T-E	Human	Esophagus	ESCC	3.16e-13	6.89e-01	0.1426
5836	PYGL	P12T-E	Human	Esophagus	ESCC	2.39e-02	2.05e-01	0.1122
5836	PYGL	P15T-E	Human	Esophagus	ESCC	2.00e-22	6.32e-01	0.1149
5836	PYGL	P16T-E	Human	Esophagus	ESCC	6.16e-17	3.39e-01	0.1153
5836	PYGL	P17T-E	Human	Esophagus	ESCC	1.03e-04	3.94e-01	0.1278
5836	PYGL	P19T-E	Human	Esophagus	ESCC	9.00e-08	1.43e+00	0.1662
5836	PYGL	P20T-E	Human	Esophagus	ESCC	6.88e-11	3.40e-01	0.1124

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:00060919	Cervix	CC	generation of precursor metabolites and energy	105/2311	490/18723	7.40e-09	6.61e-07	105
GO:00159809	Cervix	CC	energy derivation by oxidation of organic compounds	74/2311	318/18723	3.83e-08	2.53e-06	74
GO:00196939	Cervix	CC	ribose phosphate metabolic process	72/2311	396/18723	4.49e-04	4.48e-03	72
GO:00425939	Cervix	CC	glucose homeostasis	50/2311	258/18723	7.57e-04	6.76e-03	50
GO:00335009	Cervix	CC	carbohydrate homeostasis	50/2311	259/18723	8.28e-04	7.22e-03	50
GO:00463908	Cervix	CC	ribose phosphate biosynthetic process	39/2311	190/18723	9.02e-04	7.77e-03	39
GO:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0015980110	Esophagus	ESCC	energy derivation by oxidation of organic compounds	220/8552	318/18723	1.20e-17	1.09e-15	220
GO:0019693111	Esophagus	ESCC	ribose phosphate metabolic process	234/8552	396/18723	4.24e-08	7.76e-07	234
GO:0046390110	Esophagus	ESCC	ribose phosphate biosynthetic process	119/8552	190/18723	1.73e-06	2.06e-05	119
GO:00442626	Esophagus	ESCC	cellular carbohydrate metabolic process	160/8552	283/18723	1.43e-04	9.66e-04	160
GO:001605216	Esophagus	ESCC	carbohydrate catabolic process	91/8552	154/18723	5.39e-04	2.97e-03	91
GO:00973002	Esophagus	ESCC	programmed necrotic cell death	32/8552	47/18723	1.59e-03	7.43e-03	32
GO:00442751	Esophagus	ESCC	cellular carbohydrate catabolic process	27/8552	40/18723	4.39e-03	1.73e-02	27
GO:00702654	Esophagus	ESCC	necrotic cell death	39/8552	62/18723	4.68e-03	1.82e-02	39
GO:000609122	Liver	HCC	generation of precursor metabolites and energy	340/7958	490/18723	4.04e-34	2.85e-31	340
GO:001598022	Liver	HCC	energy derivation by oxidation of organic compounds	221/7958	318/18723	1.02e-22	1.86e-20	221
GO:001969322	Liver	HCC	ribose phosphate metabolic process	248/7958	396/18723	3.15e-16	2.70e-14	248
GO:001605222	Liver	HCC	carbohydrate catabolic process	99/7958	154/18723	3.79e-08	8.30e-07	99
GO:004639012	Liver	HCC	ribose phosphate biosynthetic process	116/7958	190/18723	1.79e-07	3.29e-06	116

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa049109	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa049318	Esophagus	ESCC	Insulin resistance	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0492214	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa0491014	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0493113	Esophagus	ESCC	Insulin resistance	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0492215	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa0491041	Liver	HCC	Insulin signaling pathway	95/4020	137/8465	1.53e-07	1.97e-06	1.10e-06	95
hsa0493121	Liver	HCC	Insulin resistance	77/4020	108/8465	3.89e-07	4.46e-06	2.48e-06	77
hsa0492241	Liver	HCC	Glucagon signaling pathway	64/4020	107/8465	6.70e-03	1.87e-02	1.04e-02	64
hsa0491051	Liver	HCC	Insulin signaling pathway	95/4020	137/8465	1.53e-07	1.97e-06	1.10e-06	95
hsa0493131	Liver	HCC	Insulin resistance	77/4020	108/8465	3.89e-07	4.46e-06	2.48e-06	77
hsa0492251	Liver	HCC	Glucagon signaling pathway	64/4020	107/8465	6.70e-03	1.87e-02	1.04e-02	64
hsa049108	Oral cavity	OSCC	Insulin signaling pathway	83/3704	137/8465	4.83e-05	2.00e-04	1.02e-04	83
hsa049317	Oral cavity	OSCC	Insulin resistance	60/3704	108/8465	8.66e-03	1.97e-02	1.00e-02	60
hsa0491013	Oral cavity	OSCC	Insulin signaling pathway	83/3704	137/8465	4.83e-05	2.00e-04	1.02e-04	83
hsa0493112	Oral cavity	OSCC	Insulin resistance	60/3704	108/8465	8.66e-03	1.97e-02	1.00e-02	60

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

PYGL

SNV

Missense_Mutation

novel

c.2326N>C

p.Ala776Pro

p.A776P

P06737

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-A1-A0SH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

PYGL

SNV

Missense_Mutation

c.509N>C

p.Lys170Thr

p.K170T

P06737

protein_coding

tolerated(0.28)

benign(0.091)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PYGL

SNV

Missense_Mutation

novel

c.278N>A

p.Gly93Asp

p.G93D

P06737

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A5EH-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PYGL

SNV

Missense_Mutation

rs745756440

c.2180A>G

p.Tyr727Cys

p.Y727C

P06737

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0B9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PYGL

SNV

Missense_Mutation

c.2172N>C

p.Lys724Asn

p.K724N

P06737

protein_coding

tolerated(0.36)

benign(0.007)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PYGL

deletion

Frame_Shift_Del

novel

c.1971delN

p.Ile658PhefsTer23

p.I658Ffs*23

P06737

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PYGL

SNV

Missense_Mutation

novel

c.1333N>A

p.Leu445Ile

p.L445I

P06737

protein_coding

deleterious(0.01)

possibly_damaging(0.698)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PYGL

SNV

Missense_Mutation

novel

c.873N>T

p.Glu291Asp

p.E291D

P06737

protein_coding

deleterious(0)

probably_damaging(0.975)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PYGL

SNV

Missense_Mutation

novel

c.586N>C

p.Glu196Gln

p.E196Q

P06737

protein_coding

deleterious(0.01)

probably_damaging(0.983)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

PYGL

SNV

Missense_Mutation

c.67G>C

p.Glu23Gln

p.E23Q

P06737

protein_coding

deleterious(0.05)

benign(0.025)

TCGA-DG-A2KJ-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
5836	PYGL	DRUGGABLE GENOME, ENZYME		dexamethasone	DEXAMETHASONE	23007406
5836	PYGL	DRUGGABLE GENOME, ENZYME		methotrexate	METHOTREXATE	23007406
5836	PYGL	DRUGGABLE GENOME, ENZYME		PSN357
5836	PYGL	DRUGGABLE GENOME, ENZYME		asparaginase	ASPARAGINASE	23007406

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